Bioreactors commonly have been employed for the cultivation and propagation of cells, such as mammalian cells, as well as the replication of virus-infected cells, in which the bioreactor comprises a housing in which nutrients are fed into the housing and the cells maintained under process conditions which permit cell growth and division within the housing, and, thereafter, the harvesting of the cells from the bioreactor.
It has been found that the use of a motionless mixing element, also known as a static mixing element, as a cell-culture propagator, is desirable, to enhance tissue-culture propagation within the bioreactor. For example, U.S. Pat. No. 4,296,204, issued Oct. 20, 1981, hereby incorporated by reference in its entirety, describes the advantages of employing certain motionless mixing elements in a housing, so that the surfaces of the motionless mixing element may be employed as a cell-growth surface by attachment of the cells, such as mammalian cells, to the surfaces of the motionless mixing element, typically by slow rotation of the elements within the housing. It is reported that the motionless mixing elements, such as a simple stationary baffle that utilizes the energy of the flowing fluids to produce mixing, result in consistent performance, regardless of flow rate and equipment dimensions. The employment of motionless mixing elements in bioreactors may be used to produce viral vaccines and to promote the growth and culture of mammalian cells. This U.S. patent describes particular motionless mixing elements comprised of an assembly of parallel sheets shaped to provide a plurality of channels, typically of corrugated form, which converge and diverge to form mixing cells.
The employment of motionless mixing elements in the design and scaleup of an anchorage-dependent, mammalian-cell bioreactor and in a method of cultivating also has been described recently in a publication Annals New York Academy of Sciences, "Design and Scaleup of an Anchorage-dependent Mammalian Cell Bioreactor", by Edward L. Paul, 589 (Biochem. Eng. 6), 642-9, 1990, hereby incorporated by reference in its entirety. This publication refers to the earlier cited U.S. Pat. No. 4,296,204 and sets forth test results achieved by employing Koch-Sulzer static mixing elements which are composed of titanium sheet material (Koch-Sulzer CY mixing elements), the sheets at a 45-degree angle and having a height of about 1/8th of an inch. It is stated that the test scaleup, employing the Koch-Sulzer motionless mixing sheet material, achieves uniform flow and distribution patterns over the cell surfaces, while operating at low fluid shear, and the Koch-Sulzer static mixing elements provide cell-attachment and growth surfaces for viral infection and replication in the cells.
The Koch-Sulzer static mixing elements, described in the 1990 publication, are described and claimed in U.S. patents in which motionless mixing packing elements are composed of sheets of corrugated lamellas, with the corrugations of adjacent lamellas oriented in different directions, while adjacent packing elements are angularly offset from each other. Typically the commercial embodiments, as tested and described in the publication, comprise sheet-metal materials (perforated or solid sheet metal) in a spaced-apart position, and which include a plurality of lamellas in contact with each other, and having corrugations therein, the corrugations sequentially arranged and oriented in different directions, the corrugations being disposed at an angle on a longitudinal axis, with the packing elements being angularly offset to an adjacent packing element, typically at about up to 90 degrees.
It is desirable to provide for a new and improved bioreactor containing motionless mixing elements, and to provide a method for the enhanced attachment and propagation of cells, in order to provide for enhanced production of the cultivated and propagated cells in the bioreactor.